Biomechanical properties of epithelial mesenchymal transition in idiopathic pulmonary fibrosis_Journal of Biomedical Engineering

Authors：

LI Mingyan ¹ , SUN Meihao ¹ , JIA Yuanbo ² , REN Hui ^2,3 ,  LIU Han ¹

1. Henan University of Chinese Medicine, Academy of Chinese Medicine Sciences, Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases Co-Constructed by Henan & Ministry of Education of PR China, Henan Key Laboratory of Chinese Medicine for Respiratory Disease, Zhengzhou 450016, P.R. China;
2. Bioinspired Engineering & Biomechanics Center, Xi'an Jiaotong University, Xi'an 710049, P.R. China;
3. Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, P.R. China;

Corresponding author：

Keywords：

Pulmonary fibrosis; Matrix stiffness; Mechanical stretch; Biomechanical microenvironment; Biomechanical receptors

DOI：

10.7507/1001-5515.202206016

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Idiopathic pulmonary fibrosis (IPF) is a progressive scar-forming disease with a high mortality rate that has received widespread attention. Epithelial mesenchymal transition (EMT) is an important part of the pulmonary fibrosis process, and changes in the biomechanical properties of lung tissue have an important impact on it. In this paper, we summarize the changes in the biomechanical microenvironment of lung tissue in IPF-EMT in recent years, and provide a systematic review on the effects of alterations in the mechanical microenvironment in pulmonary fibrosis on the process of EMT, the effects of mechanical factors on the behavior of alveolar epithelial cells in EMT and the biomechanical signaling in EMT, in order to provide new references for the research on the prevention and treatment of IPF.

Citation： LI Mingyan, SUN Meihao, JIA Yuanbo, REN Hui, LIU Han. Biomechanical properties of epithelial mesenchymal transition in idiopathic pulmonary fibrosis. Journal of Biomedical Engineering, 2023, 40(4): 632-637. doi: 10.7507/1001-5515.202206016 Copy

1.	Spagnolo P, Kropski J A, Jones M G, et al. Idiopathic pulmonary fibrosis: disease mechanisms and drug development. Pharmacol Ther, 2021, 222: 107798.
2.	Hadjicharalambous M R, Lindsay M A. Idiopathic pulmonary fibrosis: pathogenesis and the emerging role of long non-coding RNAs. Int J Mol Sci, 2020, 21(2): 524.
3.	Zhang C, Zhu X, Hua Y, et al. YY1 mediates TGF-β1-induced EMT and pro-fibrogenesis in alveolar epithelial cells. Respir Res, 2019, 20(1): 249.
4.	Marconi G D, Fonticoli L, Rajan T S, et al. Epithelial-mesenchymal transition (EMT): the type-2 EMT in wound healing, tissue regeneration and organ fibrosis. Cells, 2021, 10(7): 1587.
5.	Marmai C, Sutherland R E, Kim K K, et al. Alveolar epithelial cells express mesenchymal proteins in patients with idiopathic pulmonary fibrosis. Am J Physiol Lung Cell Mol Physiol, 2011, 301(1): L71-L78.
6.	Hatipoglu O F, Uctepe E, Opoku G, et al. Osteopontin silencing attenuates bleomycin-induced murine pulmonary fibrosis by regulating epithelial-mesenchymal transition. Biomed Pharmacother, 2021, 139: 111633.
7.	Salton F, Volpe M C, Confalonieri M. Epithelial-mesenchymal transition in the pathogenesis of idiopathic pulmonary fibrosis. Medicina (Kaunas), 2019, 55(4):83.
8.	Brown A C, Fiore V F, Sulchek T A, et al. Physical and chemical microenvironmental cues orthogonally control the degree and duration of fibrosis-associated epithelial-to-mesenchymal transitions. J Pathol, 2013, 229(1): 25-35.
9.	Leight J L, Wozniak M A, Chen S, et al. Matrix rigidity regulates a switch between TGF-β1–induced apoptosis and epithelial-mesenchymal transition. Mol Biol Cell, 2012, 23(5): 781-791.
10.	Marchioni A, Tonelli R, Cerri S, et al. Pulmonary stretch and lung mechanotransduction: implications for progression in the fibrotic lung. Int J Mol Sci, 2021, 22(12): 6443.
11.	Deng Z, Fear M W, Suk Choi Y, et al. The extracellular matrix and mechanotransduction in pulmonary fibrosis. Int J Biochem Cell Biol, 2020, 126: 105802.
12.	Booth A J, Hadley R, Cornett A M, et al. Acellular normal and fibrotic human lung matrices as a culture system for in vitro investigation. Am J Respir Crit Care Med, 2012, 186(9): 866-876.
13.	Zhang C, Wang S, Lau J, et al. IL-23 amplifies the epithelial-mesenchymal transition of mechanically conditioned alveolar epithelial cells in rheumatoid arthritis-associated interstitial lung disease through mTOR/S6 signaling. Am J Physiol Lung Cell Mol Physiol, 2021, 321(6): L1006-L1022.
14.	Li G, Chen S, Zhang Y, et al. Matrix stiffness regulates α-TAT1-mediated acetylation of α-tubulin and promotes silica-induced epithelial-mesenchymal transition via DNA damage. J Cell Sci, 2021, 134(2): jcs243394.
15.	Phan T H G, Paliogiannis P, Nasrallah G K, et al. Emerging cellular and molecular determinants of idiopathic pulmonary fibrosis. Cell Mol Life Sci, 2021, 78(5): 2031-2057.
16.	Heise R L, Stober V, Cheluvaraju C, et al. Mechanical stretch induces epithelial-mesenchymal transition in alveolar epithelia via hyaluronan activation of innate immunity. J Biol Chem, 2011, 286(20): 17435-17444.
17.	Parimon T, Yao C, Stripp B R, et al. Alveolar epithelial type II cells as drivers of lung fibrosis in idiopathic pulmonary fibrosis. Int J Mol Sci, 2020, 21(7): 2269.
18.	Froese A R, Shimbori C, Bellaye P S, et al. Stretch-induced activation of transforming growth factor-β1 in pulmonary fibrosis. Am J Respir Crit Care Med, 2016, 194(1): 84-96.
19.	Kuhn H, Zobel C, Vollert G, et al. High amplitude stretching of ATII cells and fibroblasts results in profibrotic effects. Exp Lung Res, 2019, 45(7): 167-174.
20.	Yang Y, Hu L, Xia H, et al. Resolvin D1 attenuates mechanical stretch-induced pulmonary fibrosis via epithelial-mesenchymal transition. Am J Physiol Lung Cell Mol Physiol, 2019, 316(6): L1013-L1024.
21.	张容, 毛璞, 傅威, 等. 机械牵张对人肺上皮细胞转分化的影响. 中华危重病急救医学, 2013, 25(8): 455-459.
22.	Tschumperlin D J, Lagares D. Mechano-therapeutics: targeting mechanical signaling in fibrosis and tumor stroma. Pharmacol Ther, 2020, 212: 107575.
23.	Wang N, Butler J P, Ingber D E. Mechanotransduction across the cell surface and through the cytoskeleton. Science, 1993, 260(5111): 1124-1127.
24.	Henderson N C, Arnold T D, Katamura Y, et al. Targeting of αv integrin identifies a core molecular pathway that regulates fibrosis in several organs. Nat Med, 2013, 19(12): 1617-1624.
25.	Decaris M L, Schaub J R, Chen C, et al. Dual inhibition of αvβ6 and αvβ1 reduces fibrogenesis in lung tissue explants from patients with IPF. Respir Res, 2021, 22(1): 265.
26.	Fu Y, Wan P, Zhang J, et al. Targeting mechanosensitive Piezo1 alleviated renal fibrosis through p38MAPK-YAP pathway. Front Cell Dev Biol, 2021, 9: 741060.
27.	Zhang Y, Jiang L, Huang T, et al. Mechanosensitive cation channel Piezo1 contributes to ventilator-induced lung injury by activating RhoA/ROCK1 in rats. Respir Res, 2021, 22(1): 250.
28.	Achanta S, Jordt S E. Transient receptor potential channels in pulmonary chemical injuries and as countermeasure targets. Ann N Y Acad Sci, 2020, 1480(1): 73-103.
29.	Hennes A, Held K, Boretto M, et al. Functional expression of the mechanosensitive PIEZO1 channel in primary endometrial epithelial cells and endometrial organoids. Sci Rep, 2019, 9(1): 1779.
30.	Van den Eynde C, de Clercq K, Vriens J. Transient receptor potential channels in the epithelial-to-mesenchymal transition. Int J Mol Sci, 2021, 22(15): 8188.
31.	Wang J, He Y, Yang G, et al. Transient receptor potential canonical 1 channel mediates the mechanical stress-induced epithelial-mesenchymal transition of human bronchial epithelial (16HBE) cells. Int J Mol Med, 2020, 46(1): 320-330.
32.	Gokey J J, Patel S D, Kropski J A. The role of Hippo/YAP signaling in alveolar repair and pulmonary fibrosis. Front Med (Lausanne), 2021, 8: 752316.
33.	Huang L S, Sudhadevi T, Fu P, et al. Sphingosine kinase 1/S1P signaling contributes to pulmonary fibrosis by activating Hippo/YAP pathway and mitochondrial reactive oxygen species in lung fibroblasts. Int J Mol Sci, 2020, 21(6): 2064.
34.	Rock J R, Barkauskas C E, Cronce M J, et al. Multiple stromal populations contribute to pulmonary fibrosis without evidence for epithelial to mesenchymal transition. Proc Natl Acad Sci U S A, 2011, 108(52): E1475-E1483.
35.	Liu Han, Wu Mian, Jia Yuanbo, et al. Control of fibroblast shape in sequentially formed 3D hybrid hydrogels regulates cellular responses to microenvironmental cues. NPG Asia Materials, 2020, 12: 45.
36.	孙美好, 金凡力, 李建生, 等. 特发性肺纤维化的生物力学特性. 医用生物力学, 2023, 38(1): 195-201.
37.	Wang Jie, Xu Lizhi, Xiang Zou, et al. Microcystin-LR ameliorates pulmonary fibrosis via modulating CD206⁺ M2-like macrophage polarization. Cell Death Dis, 2020, 11(2): 136.
38.	Andugulapati S B, Gourishetti K, Tirunavalli S K, et al. Biochanin-A ameliorates pulmonary fibrosis by suppressing the TGF-β mediated EMT, myofibroblasts differentiation and collagen deposition in in vitro and in vivo systems. Phytomedicine, 2020, 78: 153298.
39.	Pan J, Li X, Wang X, et al. MCTR1 intervention reverses experimental lung fibrosis in mice. J Inflamm Res, 2021, 14: 1873-1881.
40.	Peng L, Wen L, Shi Q F, et al. Scutellarin ameliorates pulmonary fibrosis through inhibiting NF-κB/NLRP3-mediated epithelial-mesenchymal transition and inflammation. Cell Death Dis, 2020, 11(11): 978.
41.	Wang L, Liu H, He Q, et al. Galangin ameliorated pulmonary fibrosis in vivo and in vitro by regulating epithelial-mesenchymal transition. Bioorg Med Chem, 2020, 28(19): 115663.

1. Spagnolo P, Kropski J A, Jones M G, et al. Idiopathic pulmonary fibrosis: disease mechanisms and drug development. Pharmacol Ther, 2021, 222: 107798.
2. Hadjicharalambous M R, Lindsay M A. Idiopathic pulmonary fibrosis: pathogenesis and the emerging role of long non-coding RNAs. Int J Mol Sci, 2020, 21(2): 524.
3. Zhang C, Zhu X, Hua Y, et al. YY1 mediates TGF-β1-induced EMT and pro-fibrogenesis in alveolar epithelial cells. Respir Res, 2019, 20(1): 249.
4. Marconi G D, Fonticoli L, Rajan T S, et al. Epithelial-mesenchymal transition (EMT): the type-2 EMT in wound healing, tissue regeneration and organ fibrosis. Cells, 2021, 10(7): 1587.
5. Marmai C, Sutherland R E, Kim K K, et al. Alveolar epithelial cells express mesenchymal proteins in patients with idiopathic pulmonary fibrosis. Am J Physiol Lung Cell Mol Physiol, 2011, 301(1): L71-L78.
6. Hatipoglu O F, Uctepe E, Opoku G, et al. Osteopontin silencing attenuates bleomycin-induced murine pulmonary fibrosis by regulating epithelial-mesenchymal transition. Biomed Pharmacother, 2021, 139: 111633.
7. Salton F, Volpe M C, Confalonieri M. Epithelial-mesenchymal transition in the pathogenesis of idiopathic pulmonary fibrosis. Medicina (Kaunas), 2019, 55(4):83.
8. Brown A C, Fiore V F, Sulchek T A, et al. Physical and chemical microenvironmental cues orthogonally control the degree and duration of fibrosis-associated epithelial-to-mesenchymal transitions. J Pathol, 2013, 229(1): 25-35.
9. Leight J L, Wozniak M A, Chen S, et al. Matrix rigidity regulates a switch between TGF-β1–induced apoptosis and epithelial-mesenchymal transition. Mol Biol Cell, 2012, 23(5): 781-791.
10. Marchioni A, Tonelli R, Cerri S, et al. Pulmonary stretch and lung mechanotransduction: implications for progression in the fibrotic lung. Int J Mol Sci, 2021, 22(12): 6443.
11. Deng Z, Fear M W, Suk Choi Y, et al. The extracellular matrix and mechanotransduction in pulmonary fibrosis. Int J Biochem Cell Biol, 2020, 126: 105802.
12. Booth A J, Hadley R, Cornett A M, et al. Acellular normal and fibrotic human lung matrices as a culture system for in vitro investigation. Am J Respir Crit Care Med, 2012, 186(9): 866-876.
13. Zhang C, Wang S, Lau J, et al. IL-23 amplifies the epithelial-mesenchymal transition of mechanically conditioned alveolar epithelial cells in rheumatoid arthritis-associated interstitial lung disease through mTOR/S6 signaling. Am J Physiol Lung Cell Mol Physiol, 2021, 321(6): L1006-L1022.
14. Li G, Chen S, Zhang Y, et al. Matrix stiffness regulates α-TAT1-mediated acetylation of α-tubulin and promotes silica-induced epithelial-mesenchymal transition via DNA damage. J Cell Sci, 2021, 134(2): jcs243394.
15. Phan T H G, Paliogiannis P, Nasrallah G K, et al. Emerging cellular and molecular determinants of idiopathic pulmonary fibrosis. Cell Mol Life Sci, 2021, 78(5): 2031-2057.
16. Heise R L, Stober V, Cheluvaraju C, et al. Mechanical stretch induces epithelial-mesenchymal transition in alveolar epithelia via hyaluronan activation of innate immunity. J Biol Chem, 2011, 286(20): 17435-17444.
17. Parimon T, Yao C, Stripp B R, et al. Alveolar epithelial type II cells as drivers of lung fibrosis in idiopathic pulmonary fibrosis. Int J Mol Sci, 2020, 21(7): 2269.
18. Froese A R, Shimbori C, Bellaye P S, et al. Stretch-induced activation of transforming growth factor-β1 in pulmonary fibrosis. Am J Respir Crit Care Med, 2016, 194(1): 84-96.
19. Kuhn H, Zobel C, Vollert G, et al. High amplitude stretching of ATII cells and fibroblasts results in profibrotic effects. Exp Lung Res, 2019, 45(7): 167-174.
20. Yang Y, Hu L, Xia H, et al. Resolvin D1 attenuates mechanical stretch-induced pulmonary fibrosis via epithelial-mesenchymal transition. Am J Physiol Lung Cell Mol Physiol, 2019, 316(6): L1013-L1024.
21. 张容, 毛璞, 傅威, 等. 机械牵张对人肺上皮细胞转分化的影响. 中华危重病急救医学, 2013, 25(8): 455-459.
22. Tschumperlin D J, Lagares D. Mechano-therapeutics: targeting mechanical signaling in fibrosis and tumor stroma. Pharmacol Ther, 2020, 212: 107575.
23. Wang N, Butler J P, Ingber D E. Mechanotransduction across the cell surface and through the cytoskeleton. Science, 1993, 260(5111): 1124-1127.
24. Henderson N C, Arnold T D, Katamura Y, et al. Targeting of αv integrin identifies a core molecular pathway that regulates fibrosis in several organs. Nat Med, 2013, 19(12): 1617-1624.
25. Decaris M L, Schaub J R, Chen C, et al. Dual inhibition of αvβ6 and αvβ1 reduces fibrogenesis in lung tissue explants from patients with IPF. Respir Res, 2021, 22(1): 265.
26. Fu Y, Wan P, Zhang J, et al. Targeting mechanosensitive Piezo1 alleviated renal fibrosis through p38MAPK-YAP pathway. Front Cell Dev Biol, 2021, 9: 741060.
27. Zhang Y, Jiang L, Huang T, et al. Mechanosensitive cation channel Piezo1 contributes to ventilator-induced lung injury by activating RhoA/ROCK1 in rats. Respir Res, 2021, 22(1): 250.
28. Achanta S, Jordt S E. Transient receptor potential channels in pulmonary chemical injuries and as countermeasure targets. Ann N Y Acad Sci, 2020, 1480(1): 73-103.
29. Hennes A, Held K, Boretto M, et al. Functional expression of the mechanosensitive PIEZO1 channel in primary endometrial epithelial cells and endometrial organoids. Sci Rep, 2019, 9(1): 1779.
30. Van den Eynde C, de Clercq K, Vriens J. Transient receptor potential channels in the epithelial-to-mesenchymal transition. Int J Mol Sci, 2021, 22(15): 8188.
31. Wang J, He Y, Yang G, et al. Transient receptor potential canonical 1 channel mediates the mechanical stress-induced epithelial-mesenchymal transition of human bronchial epithelial (16HBE) cells. Int J Mol Med, 2020, 46(1): 320-330.
32. Gokey J J, Patel S D, Kropski J A. The role of Hippo/YAP signaling in alveolar repair and pulmonary fibrosis. Front Med (Lausanne), 2021, 8: 752316.
33. Huang L S, Sudhadevi T, Fu P, et al. Sphingosine kinase 1/S1P signaling contributes to pulmonary fibrosis by activating Hippo/YAP pathway and mitochondrial reactive oxygen species in lung fibroblasts. Int J Mol Sci, 2020, 21(6): 2064.
34. Rock J R, Barkauskas C E, Cronce M J, et al. Multiple stromal populations contribute to pulmonary fibrosis without evidence for epithelial to mesenchymal transition. Proc Natl Acad Sci U S A, 2011, 108(52): E1475-E1483.
35. Liu Han, Wu Mian, Jia Yuanbo, et al. Control of fibroblast shape in sequentially formed 3D hybrid hydrogels regulates cellular responses to microenvironmental cues. NPG Asia Materials, 2020, 12: 45.
36. 孙美好, 金凡力, 李建生, 等. 特发性肺纤维化的生物力学特性. 医用生物力学, 2023, 38(1): 195-201.
37. Wang Jie, Xu Lizhi, Xiang Zou, et al. Microcystin-LR ameliorates pulmonary fibrosis via modulating CD206⁺ M2-like macrophage polarization. Cell Death Dis, 2020, 11(2): 136.
38. Andugulapati S B, Gourishetti K, Tirunavalli S K, et al. Biochanin-A ameliorates pulmonary fibrosis by suppressing the TGF-β mediated EMT, myofibroblasts differentiation and collagen deposition in in vitro and in vivo systems. Phytomedicine, 2020, 78: 153298.
39. Pan J, Li X, Wang X, et al. MCTR1 intervention reverses experimental lung fibrosis in mice. J Inflamm Res, 2021, 14: 1873-1881.
40. Peng L, Wen L, Shi Q F, et al. Scutellarin ameliorates pulmonary fibrosis through inhibiting NF-κB/NLRP3-mediated epithelial-mesenchymal transition and inflammation. Cell Death Dis, 2020, 11(11): 978.
41. Wang L, Liu H, He Q, et al. Galangin ameliorated pulmonary fibrosis in vivo and in vitro by regulating epithelial-mesenchymal transition. Bioorg Med Chem, 2020, 28(19): 115663.

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